Role of histone modification in transcription. Development imprinting.

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Presentation transcript:

Role of histone modification in transcription. Development imprinting.

CREB affects transcription by recruiting HATs—these acetylate histones and open up DNA for access to transcriptional machinery.

Mediators of histone modifications Mediators of histone modifications. Writers and erasers are enzymes, readers are members of the bromodomain family—acetylation. disrupting readers is proving to be a viable strategy for development of “epigenetic drugs”

Regulation of epigenetic marks by external stimuli.

Interaction between repressive marks.

Developmental Experiences Influence Later Responses to Anxiogenic Stimuli Maternal Care in Rats Alters Adult Offspring 1. Increased Glucocorticoid Receptor Expression in Hippocampus 2. Enhanced Glucocorticoid Feedback Sensitivity 3. Decreased Hypothalamic CRF expression 4. Reduced HPA axis activity in response to Stressors Impact of Maternal Care : 1. Increases activation of 5-HT7 Receptors in Offspring: Linked to Gs proteins 2. Increases expression of a transcription factor, NGFI-A,which binds to a site on a non-coding region of the Glucocorticoid Receptor gene. 3. Changes methylation state of specific sites of promotor sequence of Glucocorticoid Receptor gene. NGFI-A binding induces DNA demethylation, which will lead to increased transcription. Methylation of DNA is a major epigenetic mechanism that can influence gene transcription.

Methylation of GR exon 1. NGFI binding site is circled.

1D-cross reared offspring show methylation pattern consistent with rearing mother rather than birth mother (low 5’ methylation for L-H). No effect at 3’ site. 2C. Increased association of aceytlated histone and NGFI-A binding with GR exon 1 in high-LG/ABN reared adult offspring.